IDENTIFICATION OF THE GENES INVOLVED IN GLUCOSE-STIMULATED INSULIN SECRETION

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RIN cells are originated from rat pancreatic beta cells. After multiple rounds of passages, they lose sensitivity to glucose stimulation and subsequent insulin secretion, at least in part through diminished expression of glucokinase. Glucokinase is thought to play a major role as a glucose sensor in pancreatic beta cells. In this study, we attempted to identify genes involved in glucose-stimulated insulin secretion by the method of mRNA differential display using glucokinase-overexpressed RIN cells and untreated cells. We identified thirteen differentially expressed genes in this process. Among these genes, the expression levels of five genes were increased by overexpression of glucokinase. They include genes encoding L-type pyruvate kinase, mitochondrion, and uroporphyrinogen decarboxyrase, and unknown genes. The genes encoding calmodulin and glycosylphosphatidyl -inositol-anchored protein were down regulated. Interestingly, calmodulin has been shown to decrease insulin secretion in mouse pancreatic beta cells when overexpressed. Furthemore, the expression of L-type pyruvate kinase in liver is known to be regulated by insulin in a similar manner to glucokinase. These results suggest that the genes identified in this study might be associated with the glucose-sensing mechanism via interaction with glucokinase in pancreatic beta cells and may play crucial roles insulin secretion.